1. Field of the Invention
The present invention relates to a process for preparing bis(hydroxymethyl) compounds.
2. Description of the Background
Bis(hydroxymethyl) compounds of the formula (I): ##STR3## wherein X.sup.1 and X.sup.2 are the same or different electronegative groups, are presently used as intermediates in the preparation of UV stabilizers or radioopaque media. See, for example, EP-A2 0 220 034.
Current methods for preparing compounds of the formula I usually start from the corresponding C--H-acidic compounds of the formula (II): ##STR4## where X.sup.1 and X.sup.2 are as defined above. These compounds are reacted in aqueous reaction media in a Knoevenagel condensation.
If the reaction is carried out as described for the industrially important diethyl bis(hydroxymethyl) malonate (see (a) Gault, Rosesch; Bull. Soc. Chim. Fr. (5)4 (1937), 1411; and (b) Lenz, R. W.; Saunders, K.; Balakrishnan, T.; Macromolecules 12, 3 (1979), 392; and (c) Chang, H. M. et al.; J. Med. Chem. 34 (1991), 5, 1675) and ethyl bis(hydroxymethyl) cyanoacetate (see Tschierske, C.; bis(hydroxymethyl) cyanoacetate (see Tschierske, C.; Vorbrodt, H. -M.; Kresse, H., Zaschke, H.; Mol. Cryst. Liq. 177 (1989), 113), in aqueous solution using KHCO.sub.3, K.sub.2 CO.sub.3 or NaOH as a catalyst, the selectivities observed are indeed very good, compared with acid catalysis. Implementing the method on an industrial scale, however, entails a number of serious drawbacks, in particular relating to the removal of water and the isolation of the product.
Thus, as a rule, isolation by distillation is out of the question, due to considerable losses in product resulting from thermal decomposition. The gaseous decomposition products formed in the process (Welch, J., J. Chem. Soc. 1930 258), moreover, mean that a stable vacuum cannot be achieved. Isolating the bis(hydroxymethyl) compounds by extraction from the aqueous reaction solution is very laborious, particularly with the industrially important bis(hydroxymethyl) malonic esters where R.sup.1, R.sup.2 =--COOCH.sub.3 or --COOC.sub.2 H.sub.5, as these are highly water-soluble.
While, the diethyl bis(hydroxymethyl) malonate can be extracted from the aqueous reaction solution by being salted out with ammonium chloride, according to Organic Synthesis, 40, 27, this results in the entire nitrogen load remaining in the aqueous phase, requiring complex disposal measures. Moreover, multistage extractions mean that not only the desired products, but also considerable amounts of water pass into the organic phase. This has adverse consequences particularly in those cases where further processing of the bis(hydroxymethyl) malonic esters must be carried out under anhydrous conditions.
Since the bis(hydroxymethyl) compounds of the formula (I) are all quite polar and, consequently, readily water-soluble and somewhat thermally unstable, similar problems are also encountered with the other bis(hydroxymethyl) compounds of this formula.
Irrespective of the type of method used for isolating the bis(hydroxymethyl) compounds of the formula (I), the preparation of these compounds yields wastewater streams which are not entirely free from formaldehyde and, thus, not readily disposable. This is virtually prohibitive for the preparation of bis(hydroxymethyl) compounds of the formula (I) on an industrial scale.
Moreover, the bis(hydroxymethyl) compounds of the formula (I), being typical organic intermediates, must often be used in anhydrous form, in order to achieve high yields or utilize simple procedures in subsequent reactions, e.g. the reaction to 2-substituted 1,3-dioxane-5,5-dicarboxylic acid derivatives in accordance with a currently pending German patent application.
Anhydrous processes have also been disclosed. For example, the preparation of diethyl bis(hydroxymethyl) malonate by reacting diethylmalonate with paraformaldehyde in acetic acid in the presence of copper acetate at comparatively high temperatures has been described (Japan. patent appl. 072564), where the laborious removal of water is, of course, avoided. However, O-acetylated and non-acetylated compounds are produced in a mixture which can only be separated with difficulty, and the selectivity for the desired non-acetylated compound is low (Kunichika, S.; Oka, S.; Sugiyama, T.; Nakamura, K.; Fukui, K.; Nippon Kagaku Kaishi 3 (1972), 596). Moreover, the use of reaction temperatures above 50.degree. C., which are required for a satisfactory space-time yield, results in considerable product losses by thermal decomposition and by the formation of diethyl methylenemalonate.
It is also known that malonitrile can be reacted in glacial acetic acid, in the presence of potassium acetate, with gaseous formaldehyde at 100.degree. C. to produce bis(methylol) malonitrile (Ardis, A. E.; Averill, S. J.; Gilbert, H.; Miller, F. F.; Schmidt, R. F.; Stewart, F. D.; and Trumbull, H. L.; J. Am. Chem. Soc., 72 (1950), 1305), although the yield is only 24% of the theoretical yield.
There, a need exists for a process for the bis-hydroxymethylation of compounds of the above formula (II), which affords high yields of the corresponding bis(hydroxymethyl) compounds of the above formula (I) which can be further reacted with high yields, either in the pure form or alternatively in a reaction mixture, and which process does not produce any wastewater containing salts, such as ammonium salts, for example, and/or formaldehyde.